American Association of Clinical Endocrinology Disease State Clinical Review: Evaluation and Management of Immune Checkpoint Inhibitor-Mediated Endocrinopathies: A Practical Case-Based Clinical Approach

Abstract

Objective: The aim of this case-based clinical review was to provide a practical approach for clinicians regarding the management of patients with immune checkpoint inhibitor (ICI)-mediated endocrinopathies.

Methods: A literature search of PubMed, Embase, and Scopus was conducted using appropriate keywords. The discussions and strategies for the diagnosis and management of ICI-mediated endocrinopathies are based on evidence available from prospective, randomized clinical studies; cohort studies; cross-sectional studies; case-based studies; and an expert consensus.

Results: Immunotherapy with ICIs has transformed the treatment landscape of diverse types of cancers but frequently results in immune-mediated endocrinopathies that can cause acute and persistent morbidity and, rarely, death. The patterns of endocrinopathies differ between the inhibitors of the cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 or programmed cell death protein 1 ligand pathways but most often involve the thyroid and pituitary glands. The less common but important presentations include insulin-deficient diabetes mellitus, primary adrenal insufficiency, primary hypoparathyroidism, central diabetes insipidus, primary hypogonadism, and pancreatitis, with or without subsequent progression to diabetes mellitus or exocrine insufficiency.

Conclusion: In recent years, with increasing numbers of patients with cancer being treated with ICIs, more clinicians in a variety of specialties have been called upon to diagnose and treat ICI-mediated endocrinopathies. Herein, we reviewed case scenarios of various clinical manifestations and emphasized the need for a high index of clinical suspicion by all clinicians caring for these patients, including endocrinologists, oncologists, primary care providers, and emergency department physicians. We also provided diagnostic and therapeutic approaches for ICI-induced endocrinopathies and proposed that patients on ICI therapy be evaluated and treated by a multidisciplinary team in collaboration with endocrinologists.

Keywords: adrenalitis; diabetes mellitus; endocrinopathy; hypophysitis; immune checkpoint inhibitor; thyroiditis.